Studies relevant to insulin release, on intact rat islets will include: (a) measurements of cyclic AMP under control and relevant test conditions. (b) measurements of cyclic GMP under control and relevant test conditions. (c) an examination of the phosphorylation of proteins under control and experimental conditions. This will be performed by 32PO4 labeling of the phosphate pool in the islets, followed by polyacrylamide gel electrophoresis to separate the proteins. Total homogenates as well as subcellular fractions will be subjected to the gel electrophoresis. (d) measurement of physiological responses to Ca ions in the presence of ionophore A23187 in the presence and absence of agents such as epinephrine and cyclic AMP, inhibitors and stimulators of insulin release. Studies on broken cell preparations from rat islets will include: (a) measurement of adenylate cyclase activity (b) measurement of guanyl cyclase activity (c) measurement of protein kinase and the effects of agents such as Ca ions and cyclic AMP. (d) measurement of phosphoprotein phosphatase activity and the effects of agents such as Ca ions and cyclic AMP.